The HUSH (human silencing hub) complex contains the H3K9me3 binding protein M-phase phosphoprotein 8 (MPP8) and recruits the histone methyltransferase SETDB1 as well as Microrchidia CW-type zinc finger protein 2 (MORC2). Functional and mechanistic studies of the HUSH complex have hitherto been centered around SETDB1 while the in vivo functions of MPP8 and MORC2 remain elusive. Here, we show that genetic inactivation of Mphosph8 or Morc2a in the nervous system of mice leads to increased brain size, altered brain architecture, and behavioral changes. Mechanistically, in both mouse brains and human cerebral organoids, MPP8 and MORC2 suppress the repetitive-like protocadherin gene cluster in an H3K9me3-dependent manner. Our data identify MPP8 and MORC2, previously linked to silencing of repetitive elements via the HUSH complex, as key epigenetic regulators of protocadherin expression in the nervous system and thereby brain development and neuronal individuality in mice and humans.
Nanodiamonds (ND) hold great potential for diverse applications due to their biocompatibility, non‐toxicity, and versatile functionalization. Direct visualization of ND by means of non‐invasive imaging techniques will open new venues for labeling and tracking, offering unprecedented and unambiguous detection of labeled cells or nanodiamond‐based drug carrier systems. The structural defects in diamonds, such as vacancies, can have paramagnetic properties and potentially act as contrast agents in magnetic resonance imaging (MRI). The smallest nanoscale diamond particles, detonation ND, are reported to effectively reduce longitudinal relaxation time T1 and provide signal enhancement in MRI. Using in vivo, chicken embryos, direct visualization of ND is demonstrated as a bright signal with high contrast to noise ratio. At 24 h following intravascular application marked signal enhancement is noticed in the liver and the kidneys, suggesting uptake by the phagocytic cells of the reticuloendothelial system (RES), and in vivo labeling of these cells. This is confirmed by visualization of nanodiamond‐labeled macrophages as positive (bright) signal, in vitro. Macrophage cell labeling is not associated with significant increase in pro‐inflammatory cytokines or marked cytotoxicity. These results indicate nanodiamond as a novel gadolinium‐free contrast‐enhancing agent with potential for cell labeling and tracking and over periods of time.
Keratin composites enable animals to hike with hooves, fly with feathers, and sense with skin. Mammalian whiskers are elongated keratin rods attached to tactile skin structures that extend the animal’s sensory volume. We investigated the whiskers that cover Asian elephant ( Elephas maximus ) trunks and found that they are geometrically and mechanically tailored to facilitate tactile perception by encoding contact location in the amplitude and frequency of the vibrotactile signal felt at the whisker base. Elephant whiskers emerge from armored trunk skin and shift from a thick, circular, porous, stiff base to a thin, ovular, dense, soft tip. These functional gradients of geometry, porosity, and stiffness independently tune the neuromechanics of elephant trunk touch to facilitate highly dexterous manipulation while ensuring whisker durability.
Mobile microrobots have been proposed as a promising approach to overcome the limitations of traditional drug/gene delivery systems. Magnetically actuated surface rolling microrobots, or magnetic surface microrollers, have shown potential for navigation in physiologically relevant environments due to their robust locomotion characteristics. Although much is known about their locomotion abilities in various environments, the full extent of their potential in medical applications has yet to be fully explored. Here, the potential of surface microrollers for combined chemo‐ and photothermal ablation therapy under medical imaging modalities is demonstrated. The surface microrollers are half‐coated with magnetic material, allowing for photothermal heating and magnetic locomotion, and loaded with a biopharmaceutics classification system (BCS) class IV anti‐cancer drug, Docetaxel (DTX), for combined therapy. Synergistic action of on‐demand photothermal ablation and the controlled release of DTX result in the efficient elimination of cancer cells. Furthermore, microrollers can be detected ex vivo with magnetic resonance imaging (MRI) and photoacoustic imaging (PA), highlighting the potential of surface microrollers for future targeted medical applications.
The most symmetric molecule, Buckminster fullerene C60, due to its unique properties, has been intensively studied for various medical and technological advances. Minimally invasive and minimally toxic treatments hold great promise for future applications. With this in mind, this research exploited the physical properties of fullerene molecules for potential therapeutic effects. Pristine fullerenes have peak absorbance in the 380–500 nm range, making them an attractive violet-blue light filter. Since spectral quality of light can affect behavior, this research used resting state functional magnetic resonance imaging (rs fMRI) and behavioral testing to directly evaluate the effects of fullerene-filtered light on brain processing and behavior in mice. The same method was used to study if hydroxyl fullerene water complexes (3HFWC), with or without fullerene-filtered light, modulated brain processing. A month-long, daily exposure to fullerene-filtered light led to decreased activation of the brain area involved in emotional processing (amygdala). Water supplemented with 3HFWC resulted in an activation of brain areas involved in pain modulation and processing (periaqueductal gray), and decreased latency to first reaction when tested with a hot plate. The combination of fullerene-filtered light with 3HFWC in drinking water led to restored sensitivity to a hot plate and activation of brain areas involved in cognitive functions (prelimbic, anterior cingulate and retrosplenial cortex). These results uncovered the potential of fullerene-filtered light to impact emotional processing and modulate pain perception, indicating its further use in stress and pain management.